The mechanisms of intestinal water and electrolyte transport, including its neurohumoral control and the role of cyclic nucleotides (cyclic AMP and cyclic GMP) in this process will be investigated in normal rabbit intestine perturbed by various compounds which alter transport and cyclic nucleotide concentration. Sodium and chloride transport will be measured with isotopic techniques with the in vitro Ussing chamber technique and with in vivo perfusion techniques in anesthetized animals. Cyclic AMP and cyclic GMP will be measured by immunoassay in intestinal tissue incubated in vitro with various transport perturbing compounds or after in vivo administration. Work in this coming year will center on the effect of large organic anions of the disulfonic stilbene class (SITS and DIDS) which have been shown to have significant effect on anion transport in other membranes such as the red cell. We will correlate the effects of these drugs with the previous studies in our laboratory on the effects of other organic anions such as acetylsalicyclic acid and phenophthalein, and will attempt to determine whether the disulfonic stilbenes effect sodium chloride transport in the intestine in a fashion similar to aspirin and phenolphthalein. These studies will give insight into the mechanism of organic anion effects on electrolyte transport in intestine. These studies will increase our understanding of electrolyte transport by the intestinal epithelium and of the pharmacology of cathartic and anti-diarrheal drugs which alter intestinal electrolyte transport.